BIOMAT Database Logo BIOMAT Database Logo

Growth inhibition of HT-29 human colon cancer cells by analogues of 1,25-dihydroxyvitamin D3. 1994

M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
Department of Surgery, Lombardi Cancer Research Center, Georgetown University Hospital, Washington, DC 20007.

The use of 1,25-dihydroxyvitamin D3 as an antiproliferative agent in the treatment of cancer is limited by its hypercalcemic effects. Analogues with equivalent or greater antiproliferative activities but smaller hypercalcemic effects have been developed. The antiproliferative effects of 1,25-dihydroxyvitamin D3 and four analogues were studied in HT-29 and SW620 human colon cancer cell lines, moderate and low expressors of the vitamin D receptor, respectively. HT-29 is a primary, moderately differentiated, cell line, while SW620 is metastatic and poorly differentiated. Growth curve studies, proliferation assays, and clonogenic assays were used to assess the antiproliferative effects of 1,25-dihydroxyvitamin D3, 1,25-dihydroxy-16-ene-23-yne-D3, 1,25-dihydroxy-26,27-hexafluoro-16-ene-23-yne-D3, 1,25-dihydroxy-16,23E-diene-26,27-hexafluoro-D3, and 1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-D3. Growth of HT-29 cells was significantly inhibited by all four analogues at 10(-8) M (P < 0.05). Analogues 1,25-dihydroxy-26,27-hexafluoro-16-ene-23-yne-D3, 1,25-dihydroxy-16,23E-diene-26,27-hexafluoro-D3, and 1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-D3 were 2 times as potent as analogue 1,25-dihydroxy-16-ene-23-yne-D3 and 1,25-dihydroxyvitamin D3. SW620 cells did not show any growth inhibition with any of the compounds tested. The affinities of the three most potent analogues for the vitamin D receptor were similar to that of 1,25-dihydroxyvitamin D3, while that of analogue 1,25-dihydroxy-16-ene-23-yne-D3 was lower. These results demonstrate that, as in leukemic cells, analogues of 1,25-dihydroxyvitamin D3 are potent antiproliferative agents in colon cancer cells and this activity is most likely mediated through the vitamin D receptor.

UI MeSH Term Description Entries
D002117 Calcitriol The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. 1 alpha,25-Dihydroxycholecalciferol,1 alpha,25-Dihydroxyvitamin D3,1, 25-(OH)2D3,1,25(OH)2D3,1,25-Dihydroxycholecalciferol,1,25-Dihydroxyvitamin D3,1 alpha, 25-dihydroxy-20-epi-Vitamin D3,1,25(OH)2-20epi-D3,1,25-dihydroxy-20-epi-Vitamin D3,20-epi-1alpha,25-dihydroxycholecaliferol,Bocatriol,Calcijex,Calcitriol KyraMed,Calcitriol-Nefro,Decostriol,MC-1288,MC1288,Osteotriol,Renatriol,Rocaltrol,Silkis,Sitriol,Soltriol,Tirocal,1 alpha,25 Dihydroxyvitamin D3,1,25 Dihydroxycholecalciferol,1,25 Dihydroxyvitamin D3,1,25 dihydroxy 20 epi Vitamin D3,Calcitriol Nefro,D3, 1 alpha,25-Dihydroxyvitamin,D3, 1,25-Dihydroxyvitamin,D3, 1,25-dihydroxy-20-epi-Vitamin,KyraMed, Calcitriol,MC 1288
D002272 Carcinoembryonic Antigen A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment. Antigens, CD66e,CD66e Antigen,Antigen, CD66e,Antigen, Carcinoembryonic,CD66e Antigens
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000469 Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured

Related Publications

M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
Enhancement of butyrate-induced differentiation of HT-29 human colon carcinoma cells by 1,25-dihydroxyvitamin D3.
November 1989, Biochemical pharmacology,
M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
Inhibition of HT-29 human colon cancer growth under the renal capsule of severe combined immunodeficient mice by an analogue of 1,25-dihydroxyvitamin D3, DD-003.
October 1994, Cancer research,
M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
Inhibition of human cancer cell growth by 1,25-dihydroxyvitamin D3 metabolites.
September 1983, Cancer research,
M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
Human colon cell line HT-29: characterisation of 1,25-dihydroxyvitamin D3 receptor and induction of differentiation by the hormone.
February 1988, Journal of steroid biochemistry,
M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
Regulation of the 1,25-dihydroxyvitamin D3 receptor by 1,25-dihydroxyvitamin D3 in intact human cancer cells.
March 1985, Endocrinology,
M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
1,25-Dihydroxyvitamin D3 receptors and human colon adenocarcinoma.
April 1991, The British journal of surgery,
M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
Growth inhibition of human breast cancer cells by 1,25-dihydroxyvitamin D3 is accompanied by induction of apolipoprotein D expression.
September 1997, Cancer research,
M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
Growth regulation of human colon cancer cells by epidermal growth factor and 1,25-dihydroxyvitamin D3 is mediated by mutual modulation of receptor expression.
December 1998, European journal of cancer (Oxford, England : 1990),
M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
Inhibition of tropoelastin expression by 1,25-dihydroxyvitamin D3.
January 1991, Connective tissue research,
M Shabahang, and R R Buras, and F Davoodi, and L M Schumaker, and R J Nauta, and M R Uskokovic, and R V Brenner, and S R Evans
Regulation of epidermal growth factor receptor levels by 1,25-dihydroxyvitamin D3 in human breast cancer cells.
May 1988, Cancer research,
Copied contents to your clipboard!